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Prospective Study on the Clinical Course and Outcomes in Transfusion-Related Acute Lung Injury*

Looney, Mark R. MD1,2; Roubinian, Nareg MD2,3; Gajic, Ognjen MD4; Gropper, Michael A. MD, PhD5; Hubmayr, Rolf D. MD4; Lowell, Clifford A. MD, PhD2; Bacchetti, Peter PhD6; Wilson, Gregory CCRP7; Koenigsberg, Monique RN2; Lee, Deanna C. PhD2; Wu, Ping MS2; Grimes, Barbara PhD6; Norris, Philip J. MD2,3; Murphy, Edward L. MD2,3; Gandhi, Manish J. MD8; Winters, Jeffrey L. MD8; Mair, David C. MD9; Schuller, Randy M. BS9; Hirschler, Nora V. MD2,10; Rosen, Rosa Sanchez MD2,3; Matthay, Michael A. MD1; Toy, Pearl MD2 for the Transfusion-Related Acute Lung Injury Study Group

doi: 10.1097/CCM.0000000000000323
Clinical Investigations
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Objective: Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases.

Design: Prospective case study with controls.

Setting: University of California, San Francisco and Mayo Clinic, Rochester.

Patients: We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury.

Interventions: None.

Measurements and Main Results: Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls.

Conclusions: In conclusion, transfusion-related acute lung injury produced a condition resembling the systemic inflammatory response syndrome and was associated with substantial in-hospital morbidity and mortality in patients with transfusion-related acute lung injury compared with transfused controls. Patients with possible transfusion-related acute lung injury had even higher in-hospital morbidity and mortality, suggesting that clinical outcomes in this group are mainly influenced by the underlying acute lung injury risk factor(s).

1Department of Medicine, University of California San Francisco, San Francisco, CA.

2Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA.

3Blood Systems Research Institute, San Francisco, CA.

4Department of Medicine, Mayo Clinic, Rochester, MN.

5Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA.

6Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.

7Department of Anesthesia, Mayo Clinic, Rochester, MN.

8Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

9American Red Cross Neutrophil Reference Laboratory, St. Paul, MN.

10Blood Centers of the Pacific, San Francisco, CA.

* See also p. 1739.

Dr. Looney received support for article research from the National Institutes of Health (NIH). He was supported by the National Heart, Lung, and Blood Institute Transfusion Medicine (NHLBI) (HL107386). His institution received grant support, support for travel, support for writing/reviewing the manuscript, and provision of writing assistance from the NIH. Dr. Roubinian received support for article research from the NIH. His institution received grant support from the NIH. Dr. Gajic received support for article research from the NIH. Dr. Gropper received support for article research from the NIH. His institution received grant support from the NHLBI. Dr. Hubmayr consulted for Philips Medical, is employed by Mayo Clinic, has stock options with Respithera (for scientific board membership), served as board member for Respithera (has stock options), and received support for article research from the NIH. His institution received grant support from the NIH. Dr. Lowell received support for article research from the NIH. His institution received grant support from the NIH. Dr. Bacchetti received support for article research from the NIH and was supported by UCSF-CTSI (grant numbers UL1 RR024131 and UL1 TR000004). His institution received grant support from the NIH. Mr. Wilson received support for article research from the NIH. His institution received grant support from the NIH. Ms. Koenigsberg received support for article research from the NIH. Her institution received grant support and support for writing/reviewing the manuscript from the NIH. Dr. Lee is employed by the University of California, San Francisco and received support for article research from the NIH. Her institution received grant support from the NIH and from the University of California, San Francisco. Dr. Wu is employed by Blood Centers of the Pacific, San Francisco, and has past employment with Immunogenetics, Foster City, and University of California, San Francisco, and he received support for article research from the NIH. His institution received grant support and support for writing/reviewing the manuscript from the NIH. Dr. Grimes is employed by University of California, San Francisco and received support for article research from the NIH. Her institution received grant support and support for writing/reviewing the manuscript from the NIH. Dr. Norris served as a board member for Charisela; provided expert testimony for Williams & Connolly, Covington & Burling, and Supple & Canvel; and received support for article research from the NIH. Dr. Gandhi received support for article research from the NIH. His institution received grant support from the NIH. Dr. Winters consulted for Grifoils (consultation on plasma exchange clinical trial design) and TerumoBCT (member of committee responsible for selection on plasma exchange grant award recipients) and received support for article research from the NIH. His institution received grant support from the NIH (transfusion-related acute lung injury [TRALI] Specialized Centers of Clinically Oriented Research [SCCOR]), Fenwal, Asahi Kasei Kuraray, Food and Drug Administration, and National Health Service and received support for travel from the NIH (TRALI SCCOR) and the American Society for Hematology. Dr. Mair received support for article research from the NIH. His institution received grant support from the NIH. Dr. Schuller received support for article research from the NIH and is employed by the American Red Cross. His institution received grant support from the NIH. Dr. Hirschler is employed by Blood Centers of the Pacific and received support for article research from the NIH. Her institution received grant support from University of California, San Francisco. Dr. Matthay consulted for Cerus (acute lung injury), Roche-Genetec (Chair, DSMB for clinical trial of asthma, DSMB for ARDS trial—trauma), and Biogen (consulting for acute respiratory distress syndrome, ARDS); received support for travel from the Intensive Care Society of France (Societe Reanimation Francaise); received support for article research from the NIH; and was supported by the NHLBI (HL51856). He and his institution received grant support from GSK (to study biomarkers in ARDS and sepsis). His institution received grant support from the NHLBI. Dr. Toy was employed by the University of California, San Francisco and received support for article research from the NIH. Her institution received grant support, and she received support for travel, support for writing/reviewing the manuscript, and support for manuscript preparation from the NIH and was supported by the NHLBI (SCCOR P50HL081027). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI or the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: mark.looney@ucsf.edu

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins